Rapid advances in the synthesis of superparamagnetic nanoparticles has stimulated widespread interest in their use as contrast agents for visualizing biological processes with Magnetic Resonance Imaging (MRI). With this approach, strong particle magnetism shortens MRI relaxation times for nearby water protons and, in turn, alters observed image contrast. Magnetic particle detection with MRI is therefore indirect and suffers from several associated problems, including - poor sensitivity and quantification, ambiguous contrast, and tissue-dependent performance. To overcome these limitations, this proposal seeks to develop and test a direct approach for Magnetic Particle Imaging (MPI) that is based on recent work by other researchers (Nature 435: 1214-1217 (2005)). Unlike MRI, which requires a costly superconducting magnet, MPI utilizes relatively inexpensive components to directly quantify the amount of superparamagnetic material at each location. In practice, this is achieved with a weak oscillating magnetic field and exploits the nonlinear response of nanoparticle magnetization to generate harmonics that are detected using an inductively coupled receiver. Spatial localization is then realized using large static magnetic field gradients so particle magnetization outside a sensitive point quickly saturates and is non-responsive. In this proposal, the engineering of MPI is described, the importance of system and particle design is elucidated, and rigorous performance estimates are validated using a prototype transceiver. Preliminary results suggest that achievable mass sensitivity, spatial resolution, and measurement time with three-dimensional (3D) MPI is comparable to or better than MRI. In addition, MPI is relatively inexpensive, meets all current safety guidelines, is quantitative, provides unambiguous contrast with tissue-independent performance, and can detect lower particle concentrations. Given these attributes, proposed work seeks to engineer, construct, and test the world's first 3D MPI system for visualizing magnetic nanoparticles in live mice. Performance will be tested using Pluronic-stabilized magnetite nanoparticles specially synthesized for maximum sensitivity and resolution. Test particles are attractive for biomedical applications since they have long half-lives in circulating blood, can be loaded with water-insoluble anticancer drugs, and can be targeted to specific tissues. Imaging results obtained with MPI are therefore anticipated to provide new insight into how magnetic nanomaterials are distributed and their potential use for targeted drug delivery. PUBLIC HEALTH RELEVANCE: Proposed work will develop a new, noninvasive imaging technique for visualizing the amount and location of magnetic nanoparticles delivered to biological tissue. The technique offers high sensitivity and resolution, is relatively inexpensive, meets all current safety guidelines, and is anticipated to serve as a new diagnostic imaging platform that exploits magnetic labels for understanding health, disease, and treatment at the nano- scale. [unreadable] [unreadable] [unreadable]